William E. Schoenlein

Electrophysiological control of ventricular rate during atrial fibrillation.

Thirteen anesthetized canine subjects (17–29 kg) were used to demonstrate that mild cervical left vagal stimulation could control ventricular rate effectively during atrial fibrillation (AF). Two studies are presented. The first study used six subjects to demonstrate the inverse relationship between (manually applied) left vagal stimulation and ventricular excitation (R wave) rate during AF. As left vagal stimulation frequency was increased, ventricular excitation rate decreased. In these studies, a left vagal stimulus frequency of 0–10 per second reduced the ventricular excitation rate from > 200/min to < 50/min. The decreasing ventricular excitation rate with increasing left vagal stimulation frequency was universal, occurring in all 26 trials with the six subjects. This fundamental principle was used to construct an automatic controller for use in the second study, in which seven subjects were used to demonstrate that ventricular rate can be brought to and maintained within a targeted range with the use of an automatic (closed‐loop) controller. A 45‐minute record of automatic ventricular rate control is presented. Similar records were obtained in all seven subjects.

Characterization of atrioventricular nodal response to electrical left vagal stimulation.

AbstractThe dynamic effect of left vagal stimulation on atrioventricular conduction was studied in six isofluorane-anesthetized dogs ranging in weight from 22 to 29 kg. The cervical vagus nerve trunks were left intact and no beta-adrenergic blockade was produced so that any influences of the sympathetic nervous system and autonomic reflex activity could be observed. Atrial pacing was used to control the heart rate while single, short trains of left vagal stimulation were delivered and timed to occur at different instants during the cardiac cycle. The magnitude of the A—V delay depended on the instant of delivery of the train of vagal stimuli during the cardiac cycle. Vagal effect curves were constructed and fit to a mathematical equation which describes the pharmacokinetic behavior of a bolus injection of a drug whose onset time is of the same order as its half-life. The three parameters of this equation have physiologic significance and are related to nerve propagation time and synaptic delay, acetylcholine concentration rise, and the acetylcholineesterase mechanism. The maximum A—V delay occurred when the short train of left vagal stimuli was applied 200–300 ms after the atrial pacing stimulus and the total effect was virtually over by 800–1000 ms.

Post-mortem Changes After Lead Extraction From the Ovine Coronary Sinus and Great Cardiac Vein

We investigated in sheep, non‐thoracotomy extraction of leads which had been chronically implanted in the right atrium (RA), coronary sinus/great cardiac vein (CS / GCV) and right ventricle (RV) for atrial implantable defibrillation. Clinical success of extraction as well as gross and histologic findings in the heart are reported. Six of nine sheep had successful extractions. The major complication was laceration of the wall of the great coronary vein with hemorrhage into the pericardial space and cardiac tamponade. Tissue damage included several reversible changes: intra‐tissue hemorrhage, thrombosis in the veins, and some necrosis of fat, vascular wall and myocardium. Myocyte necrosis was estimated as 0.03 to 0.3 grams of tissue. Osseous and cartilaginous metaplasia was more common around the RA lead than the CS/GCV lead. In cases where the lead must be removed, removal from the venous insertion site using lead extraction equipment should only be attempted with surgical back‐up for emergency thora‐cotomy to control hemorrhage in the event of vessel laceration. Safer explantation of these leads from the vein entry site will require the development of new extraction procedures.

Maintenance of atrial fibrillation in anesthetized and unanesthetized sheep using cholinergic drive.

Atrial fibrillation (AF) was induced electrically and the duration of AF was measured in six isoflurane‐anesthetized sheep (weight range 54.5–72.7 kg), and in five Unanesthetized sheep (weight range 60–75 kg). In the anesthetized sheep, AF was induced by direct electrical stimulation of the right atrium with a catheter electrode and the duration of AF was determined. Intravenous neostig‐ mine (10 fig/kg IV) was administered and the duration of AF was again measured. Then cholinergic drive was increased by bilateral electrical vagal stimulation; AF was induced and the duration of AF was measured. In the anesthetized animals with no neostigmine or vagal stimulation, 34% of the episodes of AF lasted 10 seconds, 11% lasted 20 seconds, and only 1 % lasted 200 seconds. However, in one anesthetized animal AF was sustained for 4,800 seconds with no drug or vagal support. The administration of neostigmine alone in 3 anesthetized animals more than doubled the average duration of AF. In the animals with vagal stimulation (after neostigmine), AF persisted throughout stimulation, but ceased shortly after vagal stimulation was terminated at 2,220, 4,500, and 3,840 seconds. The AF frequency ranged from 325–750/min. The Unanesthetized sheep were lightly sedated with a small dose (200 fig/kg IM) of xylazine to make them less sensitive to environmental noise; then AF was induced and its duration was timed. After these measurements, neostigmine was administered (30 μg/kg IM) and cholinergic drive was produced reflexly by intravenous injection of 60–2,000 fig of phenylephrine. AF was electrically induced at the time of maximum reflex slowing in heart rate. For the control (no drug! studies, 64% of the AF episodes lasted 10 seconds, 20% lasted 20 seconds, and only 2% of the episodes lasted as long as 140 seconds. When phenylephrine was injected after neostigmine to provide increased cholinergic drive, the duration of fibrillation depended on the dose of phenylephrine. In a 60‐kg sheep, the duration of AF increased from 1 second with an intravenous dose of 60 μg to 700 seconds with an intravenous dose of 2,000 μg. However, there was a considerable range in responsiveness to the reflex cholinergic drive provided by the intravenous phenylephrine; for example a single intravenous 500‐μg dose produced AF ranging from 190–540 seconds among the sheep. The duration of AF was most controllable in the anesthetized sheep, following neostigmine administration and with bilateral vagal stimulation. In the Unanesthetized sheep, AF could generally be sustained for more than the duration of the half‐life (about 4 minutes) of phenylephrine following neostigmine. However, there was a large variation in the duration of AF among the animals for the same dose of phenylephrine. This study identifies two methods (direct vagal stimulation and reflex vagal stimulation) for providing the cholinergic drive needed to sustain AF in the adult sheep. The duration of AF is sufficiently long to enable the measurement of electrical atrial defibriilation threshold.

Gastric insufflation during IAC-CPR and standard CPR in a canine model

This study was undertaken to determine the effect of interposed abdominal compressions (IAC) during cardiopulmonary resuscitation (CPR) on gastric insufflation when the airway is not secured with an endotracheal tube. A canine model was used in which a common ventilation pressure was applied to separate cuffed esophageal and tracheal tubes. Gas entering the stomach was collected by a pre-placed gastrostomy tube leading to a bell spirometer. Gas entering the lungs was measured with a Wright Respirometer in series with the endotracheal tube. During standard CPR, measurable gastric gas volume was collected in 28 of 30 trials (mean 215 +/- 93 ml/ventilation). During IAC-CPR, in which abdominal pressure was maintained during ventilation after every 5th chest compression, measurable gastric gas was collected in 15 of 30 trials (mean 40 +/- 11 ml/ventilation). Interposed abdominal compressions as an adjunct to standard CPR may not only be of hemodynamic benefit, but may also reduce the incidence of gastric insufflation and attendant complications.

The Chronaxie and Propagation Velocity of Canine Cervical Vagus Nerve Fibers In Vivo

A recent medical development is the stimulation of the left afferent vagus nerve to control seizures in man. It is well known that vagus nerves innervate the heart; however, when afferent fibers are stimulated so are efferent fibers. Basic to the understanding of afferent fiber stimulation is the fundamental excitability properties of the vagus nerve. In this study, we measured chronaxie, rheobase and propagation velocity in the intact dog cervical afferent vagus nerve. Five adult mongrel dogs of both sexes, weighing 22–29 kg, were sedated with thiopental sodium, intubated, and connected to an anesthesia machine delivering isoflurane and oxygen. The ventral side of the neck was dissected and two bipolar electrodes were then placed on the vagus nerve, as far from one another as possible, and data were collected in the form of the strength–duration curve using single rectangular current pulses. Two different fiber types, which we designated A and B, were identified electrophysiologically. The average values for chronaxie were 75.4 ± 24.5 μs for A fibers and 82.3 ± 23.3 μs for B fibers. Values for rheobase were 0.63 ± 0.18 mA for A fibers and 0.66 ± 0.22 mA for B fibers. Propagation velocities were 59.0 ± 9.6 m/s for A fibers and 43.4 ± 8.0 m/s for B fibers. With an effective electrode area of 5 mm2, this yields current densities of 13.0 mA/cm2 and 12.9 mA/cm2 for A and B fibers respectively. We also identified fibers in the right vagus, which we called BH, with propagation velocity of 5.75 ± 0.35 m/s, which appears to be responsible for cardiac slowing. Fibers with a high propagation velocity appeared to have a short chronaxie and fibers with a low propagation velocity appeared to have a long chronaxie; however, no definitive relationship between propagation velocity and chronaxie was found.

Self-sealing, Large Bore Arterial Punctures: A Counterintuitive New Phenomenon

The human femoral artery can bleed dangerously following the removal of a catheter uring cardiac catheterization. In this study, a modified technique of needle insertion, simply inserting the needle bevel-down instead of the standard bevel-up approach, was tested as a means to reduce bleeding after catheter removal. Large bore needle punctures were made in surgically exposed arteries of anesthetized pigs using either a standard technique (45 degree approach, bevel up) or a modified technique (25 degree approach, bevel down). For half the punctures, topical phenylephrine solution (1 mg/ml) was applied to the adventitia of the artery to cause constriction. Median bleeding rates were reduced from 81 to less than 1 ml/min/100 mmHg intraluminal pressure by the modified technique with application of phenylephrine. In most cases zero bleeding, that is self-sealing, of the arteries occurred. It is postulated that a flap-valve of tissue created by the modified technique produced this self-sealing behavior. Sophisticated modeling studies are needed to fully understand this new phenomenon.

Magnetic Stimulation of the Heart and Safety Issues in Magnetic Resonance Imaging

Our group at Purdue University has been studying the physiological effects of pulsed magnetic fields for several years. The initial work was directed toward cardiac pacing with a pulsed magnetic field. Our motivation was the development of a non-invasive and relatively pain-free method for cardiac stimulation. We were the first to induce cardiac ectopic beats with pulsed magnetic fields in the closed-chest dog [1,2]. Unfortunately, the large energies required to stimulate the heart preclude the development of a portable magnetic cardiac pacemaker.

Electroventilation with monopolar and bipolar intratracheal electrodes.

Electroventilation is the technique of producing inspiration with stimuli applied to inspiratory muscles by using strategically placed electrodes on or within the body. We conducted studies using the dog to determine the efficacy of monopolar and bipolar intratracheal electrodes for electroventilation. Bipolar electrodes were able to produce an inspired volume greater than a spontaneous tidal volume in all seven dogs, but monopolar electrodes were able to in only three of seven dogs. The intratracheal electrode has the advantage over body-surface electrodes that less current is required to produce a single tidal volume, and it has the advantage over intraesophageal electrodes that anatomical placement of the electrode is simplified. These experiments demonstrated that a bipolar electrode can be used for electroventilation.

Elimination of Pulse Deficit During Atrial Fibrillation by Left Vagal Stimulation

Six anesthetized dogs (17–25 kg) were used to test the hypotheses that low-frequency, left-vagal stimulation can be used to reduce or eliminate pulse deficit during atrial fibrillation. Atrial fibrillation was induced and sustained by rapid electrical stimulation of the right atrium using a J-lead placed in the right atrial appendage. A bipolar sleeve electrode was placed around the left vagus nerve in the cervical region and low-frequency 1-ms rectangular current pulses were applied. Pulse deficit was completely eliminated in 28 of the 29 trials and was reduced in all 29. Additionally, an increase in mean blood pressure was observed at the commencement of vagal stimulation and a decrease in mean blood pressure was observed after cessation of left vagal stimulation, when the pulse deficit reappeared. We conclude that controlled low-frequency left vagal stimulation is an effective way to eliminate the pulse deficit in atrial fibrillation.